Small molecule ferroptosis inducers
AssigneeThe Trustees of Columbia University in the City of New York
InventorsBrent R. Stockwell, Kenichi Shimada, Rachid Skouta
Life of this patent
Estimating the term…
Abstract
The present invention provides, inter alia, a compound according to formula (I): Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for regulating GPX4 in a cell and methods for inducing ferroptosis in a cell.
Claims19
A compound having the structure of formula (I):
- wherein:
- R1 is selected from the group consisting of H, and —(OCH2CH2)xOH;
- X is an integer from 1 to 6;
- and
- R2, R2′, R3, and R3′ independently are selected from the group consisting of H, C3-8cycloalkyl, and combinations thereof, or R2 and R2′ may be joined together to form a pyridinyl or pyranyl and R3 and R3′ may be joined together to form a pyridinyl or pyranyl;
- or an N-oxide, or pharmaceutically acceptable salt thereof;
- with the proviso that the compound is not
A compound having the structure of formula (II):
- wherein:
- R1 is —(OCH2CH2)xOH;
- X is an integer from 1 to 6;
- and
- R4 and R5 are independently selected from the group consisting of CH2 and O;
- or an N-oxide, or pharmaceutically acceptable salt thereof,
- or
- wherein:
- R1 is OH and (1) R4 and R5 are both O;
- or (2) R4 is CH2 and R5 is O;
- or (3) R4 is O and R5 is CH2;
- or an N-oxide, or pharmaceutically acceptable salt thereof.
A method for inducing ferroptosis in a cell comprising contacting the cell with an effective amount of a compound having the structure of formula (I):
- wherein:
- R1 is selected from the group consisting of H, OH, and (OCH2CH2)xOH;
- X is an integer from 1 to 6;
- and
- R2, R2′, R3, and R3′ independently are selected from the group consisting of H, C3-8cycloalkyl, and combinations thereof, or R2 and R2′ may be joined together to form a pyridinyl or pyranyl and R3 and R3′ may be joined together to form a pyridinyl or pyranyl;
- or an N-oxide, or pharmaceutically acceptable salt thereof.
A method for inducing ferroptosis in a cell comprising contacting the cell with an effective amount of a compound having the structure of formula (II):
- wherein:
- R1 is selected from the group consisting of OH and —(OCH2CH2)xOH;
- X is an integer from 1 to 6;
- and
- R4 and R5 are independently selected from the group consisting of CH2 and O;
- or an N-oxide, or pharmaceutically acceptable salt thereof.
A method for inducing ferroptosis in a cell comprising contacting the cell with an effective amount of a compound selected from the group consisting of:
- and combinations thereof, or an N-oxide, or pharmaceutically acceptable salt thereof.
A method for decreasing GPX4 in a cell, comprising contacting the cell with an effective amount of a compound having the structure of formula (I):
- wherein:
- R1 is selected from the group consisting of H, OH, and —(OCH2CH2)xOH;
- X is an integer from 1 to 6;
- and
- R2, R2′, R3, and R3′ independently are selected from the group consisting of H, C3-8cycloalkyl, and combinations thereof, or R2 and R2′ may be joined together to form a pyridinyl or pyranyl and R3 and R3′ may be joined together to form a pyridinyl or pyranyl;
- or an N-oxide, or pharmaceutically acceptable salt thereof.
A method for decreasing GPX4 in a cell, comprising contacting the cell with an effective amount of a compound having the structure of formula (II):
- wherein:
- R1 is selected from the group consisting of OH and —(OCH2CH2)xOH;
- X is an integer from 1 to 6;
- and
- R4 and R5 are independently selected from the group consisting of CH2 and O;
- or an N-oxide, or pharmaceutically acceptable salt thereof.
A method for decreasing GPX4 in a cell, comprising contacting the cell with an effective amount of a compound selected from the group consisting of:
- and combinations thereof, or an N-oxide, or pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.